162 articles - From Friday Dec 23 2022 to Friday Dec 30 2022
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
meta-analyses and systematic reviews
| Blood Adv |
Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population. |
| Blood Cancer J |
Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis. A minority of patients attained seroconversion after booster vaccination. Strategies to improve immune response in these severely immunosuppressed patients are needed. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
The clinical relevance of detectable plasma iron species in iron overload states and subsequent to intravenous iron-carbohydrate administration. By contrast some later assays may have promoted the donation of NTBI species to transferrin during the assay procedure, potentially underestimating NTBI levels. The levels of transferrin saturation at which NTBI species have been detectable have varied between different methodologies and between patient populations studied. |
| Ann Oncol |
Association of location of BRCA1 and BRCA2 mutations with benefit from olaparib and bevacizumab maintenance in high-grade ovarian cancer: phase III PAOLA-1/ENGOT-ov25 trial subgroup exploratory analysis. Advanced-stage BRCA-mutated HGOC patients reported PFS benefit from maintenance olaparib and bevacizumab regardless of mutation location. The benefit is particularly high for patients with mutations located in the DBD of BRCA1. Mutations located in the DBD of BRCA2 are also associated with excellent outcome. |
Clonal KEAP1 mutations with loss of heterozygosity share reduced immunotherapy efficacy and low immune cell infiltration in lung adenocarcinoma. KEAP1 C-LOH mutations are associated with an immune-excluded phenotype and worse clinical outcomes among advanced LUAD patients treated with ICIs. By contrast, survival outcomes of patients whose tumors harbored KEAP1 CD-SC mutations were similar to those with KEAP1 wild-type LUADs. |
Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study. In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC. |
Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations. Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2 (iii) definition of a set of seven 'most-actionable' cancer susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, RET) in which germline follow-up is recommended regardless of tumour type. |
Methodological and reporting standards for quality of life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit. Trials published until 1 January 2025 will have to meet the prerequisites and at least two items for crediting QoL benefit in the final ESMO-MCBS score. Trials published thereafter will have to meet al four items. |
Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial. Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events. Clinical trial registry ClinicalTrials.gov, NCT02611960. |
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN. |
| Blood |
A nanobody against the von Willebrand factor A3-domain detects ADAMTS13-induced proteolysis in congenital & acquired VWD. KB-VWF-D3.1 is thus a nanobody that detects changes in the exposure of its epitope within the collagen-binding site of the A3-domain. In view of its unique characteristics, it has the potential to be used as a diagnostic tool to investigate whether a loss of larger multimers is due to ADAMTS13-mediated proteolysis. |
Analysis of T cell Repertoire and Transcriptome Identifies Mechanisms of Regulatory T cell (Treg) Suppression of GvHD. Finally, Treg did not interfere with the induction of gene sets involved in the GvT effect. Our results shed light into the mechanisms of acute GvHD suppression by Treg and will support the clinical translation of this immunoregulatory approach. |
Banking on virus-specific T-cells (VSTS) to fulfill the need for "off the shelf" cell therapies. Here we summarize clinical outcomes to date of trials of B-VSTs used for the treatment of viral infections and malignancies, and their potential as a platform for chimeric antigen receptors targeting non-viral tumors. We will highlight the properties of VSTs that make them attractive off-the-shelf cell therapies, as well as the challenges that must be overcome before they can become mainstream. |
Biology and therapeutic targeting of molecular mechanisms in MPN. However, better understanding of MPN biology has led to the development of rationally designed therapies, with the goal of not only addressing disease complications, but also potentially modifying disease course. We review the most recent data elucidating mechanisms of disease pathogenesis, and highlight emerging therapies that target MPN on several biologic levels, including JAK2-mutant MPN stem cells, JAK and non-JAK signaling pathways, mutant calreticulin and the inflammatory bone marrow microenvironment. |
Differential diagnosis of bone marrow failure syndromes guided by machine learning. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment. |
DNA polymerase theta protects leukemia cells from metabolic-induced DNA damage. Moreover, OTK inhibitor or DPC-inducing drug etoposide enhanced anti-leukemia effect of POLq inhibitor (POLqi) in vitro and in vivo. In conclusion, we demonstrated that POLq plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde and that it can be targeted to achieve therapeutic effect. |
Flotetuzumab and other T-Cell Immunotherapies Upregulate MHC Class II Expression on Acute Myeloid Leukemia Cells. Finally, we report that FLZ-induced MHC-II upregulation is mediated by IFN- |
How I Prevent and Treat Central Nervous System Disease in Adults with Acute Lymphoblastic Leukemia. As new antibody-based immunotherapy agents have been approved for relapsed/refractory B-cell ALL, their use specifically in patients with CNS disease is an area of keen interest, both because of the potential for efficacy but also concerns of unique toxicity to the CNS. In this review, we discuss data-driven approaches for these common and challenging clinical scenarios, as well as highlight how recent findings potentially support the use of novel immunotherapeutic strategies for CNS disease. |
HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia. Importantly, this mechanism is operative in other HOXA9-dependent AML genotypes. This mechanistic insight demonstrates active HOXA9-dependent differentiation block as a potent mechanism of disease maintenance in AML, that may be amenable to therapeutic intervention via therapies targeting the HOXA9/SAFB interface and/or NuRD and HP1g activity. |
Metabolism in acute myeloid leukemia: mechanistic insights and therapeutic targets. Targeting abnormal or disease-sustaining metabolic activities in AML provides a wide range of therapeutic opportunities, ideally with enhanced therapeutic windows and robust clinical efficacy. This review highlights the dysregulation of amino acid, nucleotide, lipid, and carbohydrate metabolism in AML, explores the role of key vitamins and enzymes that regulate these processes, and provides an overview of metabolism-directed therapies currently in use or development. |
Non-steroidal anti-inflammatory drugs as a targeted therapy for bone marrow failure in Ghosal Hematodiaphyseal Dysplasia. Mass spectrometry analysis demonstrated that urinary PG metabolites were increased along with proinflammatory lipoxygenase (LOX) products 5-Hydroxyeicosatetraenoic acid and leukotriene E4. Our data show that NSAIDs at standard doses surprisingly reduced both COX and LOX products, leading to the resolution of cytopenias, and should be considered for first-line treatment for Ghosal syndrome. |
Novel insights into Hodgkin lymphoma biology by single cell analysis. about cell-to-cell interactions at single cell resolution. Applied to lymphoma, recent advances in single cell RNA sequencing have broadened opportunities to delineate previously underappreciated heterogeneity of malignant cell differentiation states and presumed cell of origin, and to describe the composition and cellular subsets in the ecosystem of the tumor microenvironment (TME). Clinical deployment of an expanding armamentarium of immunotherapy options that rely on targets and immune cell interactions in the TME, emphasizes the requirement for a deeper understanding of immune biology in lymphoma. In particular, classic Hodgkin lymphoma (CHL) can serve as a study paradigm due to its unique TME, featuring infrequent tumor cells among numerous non-malignant immune cells with significant inter- and intra-patient variability. Synergistic to advances in single cell sequencing, multiplexed imaging techniques have added a new dimension to describing cellular crosstalk in various lymphoma entities. Here, we comprehensively review recent progress utilizing novel single cell technologies with an emphasis on TME biology of CHL as an application field. The described technologies, that are applicable to peripheral blood, fresh tissues and formalin-fixed samples, hold the promise to accelerate biomarker discovery for novel immunotherapeutic approaches, and to serve as future assay platforms for biomarker-informed treatment selection including immunotherapies. |
Optimizing the value of lenalidomide maintenance by genetic profiling - an analysis of 556 Myeloma XI trial patients. Patients with isolated gain(1q) derived no benefit, and double hit MM limited benefit, regardless or risk lesions involved, from Len maintenance. Extended genetic profiling identifies patients deriving exceptional benefit from Len maintenance and should be considered for newly diagnosed patients to support management discussions along their treatment pathway. |
Oxidative DNA Damage in Reconstituting T-cells is Associated with Relapse and Inferior Survival Following Allo-SCT. The 8-ohdghi T-cells' inability to efficiently target malignant cells or to produce cytotoxic Granzyme B and IFN-g was associated with a significantly increased relapse risk and a shorter overall survival. Taken together, our novel findings could give reason to focus on bolstering DNA repair in reconstituting T-cells as a mean to improve GvL efficacy. |
Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: Biological insights and clinical advances. Here we review the clinical, genetic, and biologic features of SDS. Additionally, we present evidence supporting hematologic surveillance for SDS patients that incorporates clinical, pathologic, and molecular data to risk-stratify patients and prioritize transplant evaluation for SDS patients with high-risk features. |
Prevention of acute GVHD disease using an orthogonal IL-2/IL-2Rß system to selectively expand regulatory T-cells in vivo. Importantly, oIL2Rß Treg maintained graft-versus-tumor (GVT) responses in two distinct tumor models (A20, MLL-AF9). These data demonstrate a novel approach to enhance the efficacy of Treg cell therapy in allo-HSCT using an oIL2/oIL2Rß system that allows for selective in vivo expansion of Treg leading to GVHD protection and GVT maintenance. |
Proximity proteomics identifies septin and PAK2 as decisive regulators of actomyosin expulsion of von Willebrand factor. Genetic or pharmacological inhibition of PAK2 or septins led to inefficient release of VWF and a failure to form platelet-catching strings. This new molecular mechanism offers additional therapeutic targets for the control of thrombotic disease and is highly relevant to other secretory systems that employ exocytic actomyosin machinery. |
The OTUD1-Notch2-ICD axis orchestrates allogeneic T cell-mediated graft-versus-host disease. Dapagliflozin administration significantly prolonged the survival of aGVHD mice. The present study characterized a previously unknown role of OTUD1 in T cell-mediated allogeneic responses and provided a promising therapeutic strategy to target OTUD1 for the alleviation of aGVHD. |
The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex- mediated quiescence. Proximity labeling and confocal fluorescent microscopy studies show that CD53 interacts with DREAM-associated proteins, specifically promoting the interaction between Rbl2/p130 and its phosphatase, PP2A, effectively stabilizing p130 protein availability for DREAM binding. Together, these data identify a novel mechanism by which stressed HSCs resist continued cycling. |
Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain. Lastly, examination of the mechanical stability of each variant revealed variable AIM unfolding. Together, these studies illustrate that the heterogeneity among type 2B VWD mutations is evident in AIM-A1 fragments. |
| Blood Adv |
Adaptation of Serious Illness Care Program to be Delivered via Telehealth for Older Patients with Hematologic Malignancy. The adapted SICP may provide older patients with AML and MDS an opportunity to share what matters most to them with their care team and may assist oncologists in aligning patient care with patient values. The adapted SICP is the subject of an ongoing single-arm pilot study at the Wilmot Cancer Institute. |
Comparison of the effectiveness and safety of direct oral anticoagulants: nationwide propensity score-weighted study. In conclusion, while stroke/SE rates were similar between DOACs, rivaroxaban was associated with higher rates of major bleeding compared to other DOACs and lower rates of myocardial infarction compared to dabigatran. These results may help guide oral anticoagulant selection, especially in patients at high risk of bleeding or myocardial infarction. |
Engineering amino acid uptake or catabolism promotes CAR-T cell adaption to the tumour environment. In turn we engineer and phenotype a further generation of CAR-T cells which express functional Arginase I/Arginase II enzymes, and have enhanced CAR-T cell proliferation and anti-tumour activity. Thus CAR-T cells can be adapted to the amino acid metabolic microenvironment of cancer, a hitherto recognised but unaddressed barrier to successful CAR-T therapy. |
Enriching single-arm clinical trials with external controls: possibilities and pitfalls. The validity of the treatment effect derived from indirect comparisons heavily depends on careful methodological considerations included in the proposed 3-step procedure. Because the level of evidence of a well-conducted RCT cannot be guaranteed, the evaluation is more important than in standard settings. |
External validation of the PEGED diagnostic algorithm for suspected pulmonary embolism in an independent cohort. Compared to standard algorithms, the PEGeD decreased the number of CTPA examinations. However, caution is required in patients with a low C-PTP and a D-dimer< 1000ng/mL but above their age-adjusted D-dimer cutoff. |
IL3-zetakine combined with a CD33 costimulatory receptor as a Dual CAR approach for safer and selective targeting of AML. Cytokine-Induced Killer (CIK) cells, co-expressing a first-generation low affinity anti-CD123 IL3-zetakine and an anti-CD33 as costimulatory receptor (CCR) without activation signaling domains, demonstrated a powerful antitumor efficacy against AML targets without any relevant toxicity on HSPCs and endothelial cells. The proposed optimized Dual CAR CIK strategy could offer the opportunity to unleash the potential of specifically target CD123+/CD33+ leukemic cells while minimizing toxicity against healthy cells. |
INR and vitamin K-dependent factor levels after vitamin K antagonist reversal with 4F-PCC or plasma. However, following plasma administration, mean activity levels for factors II and X were below 50% at al time points assessed within 3 hours after starting the infusion, regardless of post-infusion INR value. This retrospective analysis demonstrated that treatment with 4F-PCC in VKA-treated patients rapidly restores VKDFs to hemostatic levels irrespective of post-infusion INR value whereas plasma does not. |
Obstetric and peri-operative management of patients with Factor XI deficiency: a retrospective observational study. There were no cases of epidural or spinal hematomas associated with neuraxial anesthesia. FXI levels remain stable during pregnancy and repeat measurements may not be necessary. |
Outcomes before and after providing interdisciplinary hematology and pulmonary care for children with sickle cell disease. Lactate dehydrogenase and white blood cell counts also significantly decreased. Implementing a multidisciplinary SCD-pulmonary clinic is feasible and may allow improved management of pulmonary problems and lead to improvements in health and acute care utilization. |
Polatuzumab vedotin with infusional chemotherapy (Pola-DA-EPCH-R) for untreated aggressive B-cell non-Hodgkin lymphomas. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety endpoint. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. |
Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma. Two responders, but none of the non-responders, exhibited elevated cytokine levels post lete-cel infusion. Lete-cel had a manageable safety profile consistent with other lete-cel studies and demonstrated clear but transient antitumor activity in patients with RRMM. |
The role of Th17 cells in chronic lymphocytic leukemia: friend or foe? Herein, we also address the available data regarding the effects of CLL targeted therapies on Th17 cells, and the potential of using these cells in adoptive cell therapies. Having a sound understanding of the role played by Th17 in CLL is crucial for designing novel therapies that can achieve immune homeostasis and maximize clinical benefits. |
Venetoclax treatment in cancer patients has limited impact on circulating T and NK cells. By contrast, there was less impact on circulating T cells and natural killer (NK) cells, with no changes in their subset composition, transcriptome or function following venetoclax treatment. Our data indicate that venetoclax has minimal impact on circulating T or NK cells, supporting the rationale of combining this BH3 mimetic drug with cancer immunotherapies for more durable anti-tumour responses. |
| Blood Cancer J |
In-depth analysis of alternative splicing landscape in multiple myeloma and potential role of dysregulated splicing factors. We have developed a web portal that allows custom alternative splicing event queries by using gene symbols and visualizes AS events in MM and subgroups. Our portals can be accessed at and . |
Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation. In our study, the newly added group of patients with myelodysplasia-related gene mutations did not have adverse outcomes. Re-classifying these patients into the intermediate risk group and adjusting the grouping for al AML patients by MRD at HSCT, led to a refined and improved risk stratification, which should be validated in independent studies. |
Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. Of those who received DEC |
| Haematologica |
A novel next-generation sequencing capture-based strategy to report somatic hypermutation status using genomic regions downstream to immunoglobulin rearrangements. Overall, 84/95 (88.4%) CLL cases with conventional SHM data showed concordant SHM status, increasing to 91.6% when excluding borderline cases. Additionally, IGHJ-E mutation analysis in a wide range of pre- and post-germinal centre LPD showed significant correlation with differentiation and lineage status, suggesting that IGHJ-E analysis is a promising surrogate marker enabling SHM to be reported using NGS-capture strategies and whole genome sequencing. |
A phase 2, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Overall survival rates at Day 180 post-transplant were similar between arms, as were the rates of serious treatment-emergent adverse events (defibrotide: 42%, SOC: 44%). While the observed differences in endpoints between the two arms were not substantial, these results suggest defibrotide prophylaxis may add a benefit to currently available SOC to prevent aGvHD following allo-HCT without adding significant toxicities. |
Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to PI, IMiD and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice. Patients treated with cilta-cel experienced more adverse events vs RWCP (any grade:100% vs 83.5%). Results from this study demonstrate improved efficacy outcomes of cilta-cel vs RWCP and highlight its potential as a novel and effective treatment option for patients with TCE-MM. |
CCRL2 affects the sensitivity of myelodysplastic syndrome and secondary acute myeloid leukemia cells to azacitidine. In conclusion, we demonstrate that CCRL2 modulates epigenetic regulatory pathways, particularly DNMT levels, and affects MDS/sAML azacitidine sensitivity. These results support CCRL2 targeting as having MDS/sAML therapeutic potential. |
Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup. Finally, ES-based Copy Number Variant (CNV) analysis disclosed an unexpected high prevalence of RUNX1 deletions, predisposing to hematological malignancies. Our findings demonstrate that ES, including CNV analysis, can substantially contribute to the diagnosis of IT and can solve diagnostic problems that would otherwise remain a challenge. |
Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high dose chemotherapy independent of MIPI and complement established high-risk factors. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry-based assessment of CPT1A can contribute to defining high-risk MCL. |
Reduced platelet glycoprotein Iba shedding accelerates thrombopoiesis and COX-1 recovery: implications for aspirin dosing regimen. A cluster of clinical markers, including younger age, non-alcoholic fatty liver disease, visceral obesity and higher thrombopoietin/glycocalicin ratio, predicted with significant accuracy the likelihood of faster COX-1 recovery and suboptimal aspirin response. Circulating thrombopoietin/glycocalicin ratio, reflecting a dysregulation of platelet lifespan and production, may provide a simple tool to identify patients amenable to more frequent aspirin daily dosing. |
Targeting TPO-independent strategy in the discovery of a novel megakaryocytopoiesis inducer DMAG for treatment of thrombocytopenia. In summary, we establish a drug screening model through gcForest and demonstrate DMAG promotes megakaryocyte differentiation via the ERK/HIF1/NF-E2 pathway, which is more importantly independent of the TPO/c-MPL classic pathway. The present study may provide new insights into drug discovery for thrombopoiesis, TPO-independent regulation of thrombopoiesis and a promising avenue for thrombocytopenia treatment. |
| Lancet Haematol |
Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial. Interpretation KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction. Funding Cancer Research UK and Amgen. |
| Leukemia |
Asxl1 deletion disrupts MYC and RNA polymerase II function in granulocyte progenitors. However, Asxl1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator in myeloid development. |
Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management. |
Dual inhibition of CHK1/FLT3 enhances cytotoxicity and overcomes adaptive and acquired resistance in FLT3-ITD acute myeloid leukemia. Moreover, 30 showed favorable druggability without significant blood toxicity or myelosuppression and exhibited a good oral PK profile with a T over 12 |
Inhibition of CD39 unleashes macrophage antibody-dependent cellular phagocytosis against B-cell lymphoma. Furthermore, the addition of a CD39 inhibitor to anti-CD20 and anti-CD47 combination therapy significantly improved survival in a disseminated model of aggressive B-cell lymphoma, supporting the benefit of dual targeting CD39-mediated eATP hydrolysis and CD47-mediated "don't eat me" signal. Together, preventing eATP degradation may be a potential approach to unleash macrophage-mediated anti-lymphoma immunity. |
Integrative genomic analysis of childhood acute lymphoblastic leukaemia lacking a genetic biomarker in the UKALL2003 clinical trial. An inferior outcome for patients with ABL-class fusions (n |
Microenvironmental CXCL12 deletion enhances Flt3-ITD acute myeloid leukemia stem cell response to therapy by reducing p38 MAPK signaling. p38 inhibition in combination with chemotherapy plus TKI treatment leads to greater depletion of Flt3-ITD AML LSC compared with CXCL12 deletion. Our studies support roles for CXCL12 and p38 signaling in microenvironmental protection of AML LSC and provide a rationale for inhibiting p38 signaling to enhance Flt3-ITD AML targeting. |
Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia. Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML. |
Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients. |
Recurrent germline variant in ATM associated with familial myeloproliferative neoplasms. Structural protein modeling of this variant suggested stabilization of inactive ATM dimer, and alteration of the endogenous ATM locus in a human myeloid cell line resulted in decreased phosphorylation of the downstream tumor suppressor CHEK2. These results implicate ATM, and the DNA-damage response pathway, in predisposition to MPN. |
Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters. Accordingly, MAC (ideally based on TBI) should be preferred for alloHCT recipients with BPDCN. In patients who are not elegible for MAC alloHCT, autoHCT could be considered. |
Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed/refractory acute myeloid leukemia. Furthermore, we identified that LGALS1 was a promising target for chemoresistant AML, and LGALS1 inhibitor could help eliminate QSCs and enhance the chemotherapy in patient-derived primary AML cells, cell lines, and AML xenograft models. Our results will facilitate a better understanding of the AML chemoresistance mechanism and the development of novel therapeutic strategies for relapsed/refractory AML patients. |
| Thromb Haemost |
Drug-Drug Interaction between Antiplatelet Therapy and Lipid-Lowering Agents (Statins and PCSK9 Inhibitors). PCSK9 antibodies target a serine protease (PCSK9), which promotes the degradation of the LDL-C receptor impacting on LDL-C plasma levels and (ox)LDL-C-receptor-mediated signaling in platelets similar to but more potent than statins. These functionally synergistic actions are the basis for numerous interactions between antiplatelet and these lipid-lowering drugs, which may, in summary, reduce the incidence of atherothrombotic vascular events. |
Increased Cancer Risk in Patients with Kidney Disease and Venous Thromboembolism: A Population-Based Cohort Study. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3-1.6) when compared with the general population, and 1.1 (95% CI: 0.9-1.2) compared with VTE patients without kidney disease. Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis. |
SARS-CoV-2 vaccination: Long-Term Follow-up of Pre-Existing and De Novo Immune Thrombocytopenia (ITP). Among 11 patients who received rescue treatment, 7 had pre-existing, difficult-to-control ITP; exacerbations in these 7 may not have been caused by the vaccine. Six separate patients with de novo ITP post-SARS-CoV-2 vaccine who were followed for a median of 11 months (range 3-15) responded well to standard treatments for ITP and had favorable longer-term outcomes. |
Survival Implications of Thrombus Recurrence or Bleeding in Cancer Patients Receiving Anticoagulation for Venous Thromboembolism Treatment. Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
| Blood |
| Haematologica |
Biosimilars in rare diseases - a focus on paroxysmal nocturnal hemoglobinuria. As prescription drug spending has increased and exclusivity periods have expired, manufacturers have developed biosimilars-biologics that may be more affordable and highly similar to a licensed biological therapeutic, with no clinically meaningful differences in safety or efficacy. With biosimilars gaining regulatory approval around the globe and broadening patient access to biologics, this review aims to help rare disease healthcare providers familiarize themselves with biosimilars, understand their development and regulatory approval process, and address practical considerations that may facilitate their use. |
| Lancet Haematol |
| Leukemia |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| Haematologica |
| J Hematol Oncol |
A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. Mechanistically, we found that tRF-3022b binds to galectin 1 (LGALS1) and macrophage migration inhibitory factor (MIF) in CRC cells and reduces polarization by regulating MIF in M2 macrophages. In conclusion, our study revealed the expression pattern of tRFs in both tissue and plasma exosomes and identified a novel tRF, tRF-3022b, which may affect CRC tumor growth and M2 macrophage polarization by binding to LGALS1 and MIF. |